Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Improving Anti-malarial Treatment Options in Guinea-Bissau - Part A

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01704508
Recruitment Status : Unknown
Verified December 2013 by Bandim Health Project.
Recruitment status was:  Recruiting
First Posted : October 11, 2012
Last Update Posted : December 6, 2013
Sponsor:
Collaborator:
Karolinska Institutet
Information provided by (Responsible Party):
Bandim Health Project

Brief Summary:

Plasmodium falciparum causes malaria and approximately 665 000 deaths each year. chloroquine and sulphadoxine-pyrimethamine resistant P. falciparum are widespread. An artemisinin derivative combined with lumefantrine, amodiaquine or piperaquine is therefore recommended for the treatment of malaria in Africa. However, artemisinin resistance appears to be developing and resistance/tolerance to amodiaquine and lumefantrine exists. We are presently conducting a study in Guinea-Bissau. Preliminary data indicates that the effectiveness and availability of artemether-lumefantrine (AL), the 1st line drug, is poor. Consequently there is a need for another treatment option. Dihydroartemisinin-piperaquine (DP) has been shown to be efficacious and well tolerated in several African countries and is therefore such an option. A clinical trial comparing the safety and efficacy of artemether-lumefantrine and dihydroartemisinin-piperaquine is therefore needed.

Parents to children seeking Bandim Health Centre (CSB) with symptoms compatible with malaria will be informed of the study. If accepting and the child fulfil the inclusion criteria, the child will be randomised to treatment with either AL or DP. The treatment will be given supervised at the health centre in the morning and the evening on day 0, day 1, and day 2.

At each visit and in the morning on day 3, the child will be examined, the mother asked for any symptoms and signs of side-effects, the temperature measured. Furthermore, a blood sample will be taken for examination of malaria parasites. On day 0 samples for measurement of antimalarial drugs and for genotyping of the parasites will be taken on filterpaper. In a subgroup of 50 children a blood sample for in vitro culturing and for analysis of the number of leucocytes will also be taken.

After having finished the treatment the children will be followed on day 7 and then once a week until day 42. At each visit the condition of the child will be examined and a bloodsample taken for examination of parasites in the blood. Furthermore, a filterpaper bloodsample will be collected for measurement of the drug concentration of if the child has recrudescence for genotyping of the parasites. On day 0, 3 and 42 the haemoglobin level will be examined.

The result of the two treatments will be evaluated by comparing the number of children with recurrent parasitaemia, both corrected and uncorrected (recrudescence vs. reinfections). This will be presented as adequate clinical and parasitological response rates PCR-corrected and PCR-uncorrected. Furthermore, the chance in haemoglobin level from day 0 till day 3 and till day 42 will be compared. The concentration of the antimalarial drug in the blood samples taken at the visit before the re-parasitaemia will be capered to the concentrations in children without re-parasitaemia.

Assuming a 20% loss to follow up a total of 346 children should be included. For the children included, health care and medications at Bandim Health Centre will be free during the study period but no other gifts or payments will be made.

Results will be presented to the staff at the Bandim health centre and the ministry of Health and will be published in an international peer reviewed journal.


Condition or disease Intervention/treatment Phase
Malaria Drug: Artemether-lumefantrine Drug: Dihydroartemisinin-piperaquine Phase 4

  Show Detailed Description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 346 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Efficacy and Safety of Artemether + Lumefantrine and Dihydroartemisinin + Piperaquine for the Treatment of Uncomplicated Malaria in Guinea-Bissau.
Study Start Date : November 2012
Estimated Primary Completion Date : April 2014
Estimated Study Completion Date : January 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria

Arm Intervention/treatment
Active Comparator: Artemether-lumefantrine
6-dose regime will be used:
Drug: Artemether-lumefantrine
Other Name: Coartem (R)

Active Comparator: Dihydroartemisinin-piperaquine
A 3 dose regime will be used
Drug: Dihydroartemisinin-piperaquine
Other Name: Eurartesim




Primary Outcome Measures :
  1. Adequate clinical and parasitological response rate [ Time Frame: 42 days ]
    The data will be analysed using survival estimates of per protocol treatment failure rates but also intention to treat treatment failure rates.


Secondary Outcome Measures :
  1. the safety of AL and DP [ Time Frame: 42 days ]
    Self-reported signs and symptoms, clinical evaluations during treatment, day 7 and then weekly until day 42. leucocytes day 0, 3, 7, 14 and 21.


Other Outcome Measures:
  1. To determine the capacity of each drug combination to protect against re-infection and to differentiate recrudescence from re-infections using PCR based methods [ Time Frame: 42 days ]
  2. Genetic polymorphisms in P. falciparum causing reparasitaemia (by PCR) and in 50 children perform a characterisation of P. falciparum geno- and phenotypes. [ Time Frame: 42 days ]
    For all children with re-parasitaemia genetic polymorfisms will be established by PCR, and in additional 50 children further characterisation using cultures will be done

  3. haemoglobin values [ Time Frame: days 0, 3 and 42 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   6 Months to 12 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

A) Age ≥6 months, and <13 years. B) Mono-infection with P. falciparum detected by microscopy. C) Parasitemia of 1.000-200.000/µl asexual forms. D) Axillary temperature ≥37.5 ˚C or a history of fever within 24 hours. E) Ability to swallow oral medication.

F) Ability and willingness to comply with the study protocol for the duration of the study and to comply with the study visit schedule. G) Informed consent from a parent or guardian

-

Exclusion Criteria:

A) Signs or symptoms of severe malaria, incl. hyperparasitaemia (>200.000/ µl asexual forms) B) Presence of general danger signs in children under 5 C) Presence of severe malnutrition. D) Any evidence of chronic disease or acute infection other than malaria. E) Regular medication which may interfere with antimalarial pharmacokinetics. F) History of hypersensitivity reactions or contraindications to AL, DP or quinine.

G) Domicile outside the study area.

-


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01704508


Contacts
Layout table for location contacts
Contact: Poul-Erik Kofoed, M.D., Ph.D. +45 76363490 ext 7706 poul.erik.kofoed@slb.regionsyddanmark.dk
Contact: Johan Ursing, M.D., Ph.D. +46 704751530 johan.ursing@karolinska.se

Locations
Layout table for location information
Guinea-Bissau
Bandim Health Project Recruiting
Bissau, Guinea-Bissau
Contact: Amabelia Rodrigues, MD, ph.d.       a.rodrigues@bandim.org   
Principal Investigator: Amabelia Rodrigues, MD, ph.d.         
Sponsors and Collaborators
Bandim Health Project
Karolinska Institutet

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Bandim Health Project
ClinicalTrials.gov Identifier: NCT01704508     History of Changes
Other Study ID Numbers: Eurartesim-2012
First Posted: October 11, 2012    Key Record Dates
Last Update Posted: December 6, 2013
Last Verified: December 2013

Keywords provided by Bandim Health Project:
Falciparum malaria
children
treatment

Additional relevant MeSH terms:
Layout table for MeSH terms
Malaria
Protozoan Infections
Parasitic Diseases
Lumefantrine
Artemether
Piperaquine
Artemether, Lumefantrine Drug Combination
Dihydroartemisinin
Artemisinins
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents